Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy

This study has been completed.

Sponsor:

Collaborators:

Families of Spinal Muscular Atrophy

Sigma Tau Pharmaceuticals, Inc.

Abbott

Information provided by:

University of Utah

ClinicalTrials.gov Identifier:

NCT00374075

First received: September 6, 2006

Last updated: September 11, 2006

Last verified: September 2006

History of Changes

Purpose

This is an open label phase I/II clinical trial to assess safety, tolerability and potential effect on SMN mRNA and protein in vivo of a compound in which preliminary evidence supports a potential effect on SMN levels in vitro.

Condition	Intervention	Phase
Spinal Muscular Atrophy	Drug: Valproic Acid	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy

Resource links provided by NLM:

Genetics Home Reference related topics: spinal muscular atrophy

MedlinePlus related topics: Spinal Muscular Atrophy

Drug Information available for: Valproic acid Valproate sodium Divalproex sodium

Genetic and Rare Diseases Information Center resources: Spinal Muscular Atrophy

U.S. FDA Resources

Further study details as provided by University of Utah:

Primary Outcome Measures:

To assess safety and tolerability of VPA in SMA patients greater than 2 years of age

Secondary Outcome Measures:

To look for a potential in vivo effect of VPA on SMN mRNA in patient blood cells at routinely used clinical doses
Measures of gross motor function
Electrophysiologic measures of denervation
DEXA estimates of body composition, bone mineral density and content
Measures of pulmonary function


Estimated Enrollment:	42
Study Start Date:	September 2003
Estimated Study Completion Date:	February 2006

Detailed Description:

This is an open label phase I/II trial of valproic acid in 40 SMA subjects > 2 years of age with severe, intermediate, and mild phenotypes. Primary outcome measures includes laboratory and physical examination assessments to monitor effects on liver, hematologic, metabolic and nutritional status. Secondary outcomes includes measures of gross motor function; electrophysiologic measures of denervation; DEXA estimates of body composition, bone mineral density and content; measures of pulmonary function; and quantitative SMN mRNA and protein levels in blood cells. Subjects will need 2-3 baseline visits over a 3 -6 month period prior to enrollment. Follow-up visits will be scheduled at 3, 6 and 12 months on treatment.

Eligibility


Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have a diagnosis of SMA, confirmed by genetic testing
Only patients 2 years of age and older at enrollment will be eligible

Exclusion Criteria:

Patients taking any medications with known hepatotoxicity, congenital metabolic disorders or on multiple anticonvulsant medications
Patients taking medications which may interact with VPA
Patients on ventilatory support for more than 16 hours per day
Patients currently enrolled in other treatment trials

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00374075

Locations


United States, Utah
University of Utah/Primary Children's Medical Center
Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

University of Utah

Families of Spinal Muscular Atrophy

Sigma Tau Pharmaceuticals, Inc.

Abbott

Investigators


Principal Investigator:	Kathryn J Swoboda, M.D	University of Utah/Primary Children's Medical Center

More Information

Additional Information:

"Click here for more information about this study" This link exits the ClinicalTrials.gov site

Publications:

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Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, McPherson JD. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999 Jul;8(7):1177-83.

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Monani UR, Sendtner M, Coovert DD, Parsons DW, Andreassi C, Le TT, Jablonka S, Schrank B, Rossoll W, Prior TW, Morris GE, Burghes AH. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet. 2000 Feb 12;9(3):333-9. Erratum in: Hum Mol Genet. 2007 Nov 1;16(21):2648. Rossol, W [corrected to Rossoll, W].

Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002 Feb;70(2):358-68. Epub 2001 Dec 21.

Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AH, Prior TW. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002 Jan-Feb;4(1):20-6. doi: 10.1097/00125817-200201000-00004.

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Andreassi C, Jarecki J, Zhou J, Coovert DD, Monani UR, Chen X, Whitney M, Pollok B, Zhang M, Androphy E, Burghes AH. Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients. Hum Mol Genet. 2001 Nov 15;10(24):2841-9.

Brichta L, Hofmann Y, Hahnen E, Siebzehnrubl FA, Raschke H, Blumcke I, Eyupoglu IY, Wirth B. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet. 2003 Oct 1;12(19):2481-9. Epub 2003 Jul 29.

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ClinicalTrials.gov Identifier:	NCT00374075 History of Changes
Other Study ID Numbers:	11893
Study First Received:	September 6, 2006
Last Updated:	September 11, 2006
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Utah:


Spinal Muscular Atrophy (SMA) Valproic Acid

Additional relevant MeSH terms:


Atrophy Muscular Atrophy Muscular Atrophy, Spinal Spinal Cord Diseases Central Nervous System Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neurologic Manifestations Neuromuscular Diseases Neuromuscular Manifestations Pathological Conditions, Anatomical Signs and Symptoms Valproic Acid	Anticonvulsants Antimanic Agents Central Nervous System Agents Central Nervous System Depressants Enzyme Inhibitors GABA Agents Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Pharmacologic Actions Physiological Effects of Drugs Psychotropic Drugs Therapeutic Uses Tranquilizing Agents

ClinicalTrials.gov processed this record on February 27, 2015

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